Large Variations of Plasma Levels During Maintenance Treatment with Depot Neuroleptics

1996 ◽  
Vol 169 (5) ◽  
pp. 618-621 ◽  
Author(s):  
Eva Tuninger ◽  
Sten Levander
Keyword(s):  
Side Effects ◽  
Plasma Level ◽  
Plasma Levels ◽  
Clinical Effect ◽  
Clinical Symptoms ◽  
Repeated Measurements ◽  
Neuroleptic Treatment ◽  
Neuroleptic Medication ◽  
Depot Neuroleptics ◽  
Depot Neuroleptic

BackgroundStability of neuroleptic medication has been associated with optimal clinical effect and minimal side-effects. Depot administration is assumed to yield better stability.MethodThirty patients on depot neuroleptic treatment were followed during three years with repeated measurements of plasma level and concurrent ratings of clinical symptoms and side-effects.ResultsOf 120 blood samples 35 (29%) measurements were outside ± 2 s.d. measurement error (expected 5%). Perphenazine levels were more variable (46%) than haloperidol (25%) and flupenthixol (12.5%). No relationship was found between side-effect ratings and fluctuations of plasma levels.ConclusionDepot neuroleptic medication does not eliminate a clinically unwanted and sometimes marked variation in plasma level.

Long-term pharmacokinetics of clozapine

1998 ◽  
Vol 173 (4) ◽  
pp. 341-344 ◽  
Author(s):  
Martin Kurz ◽  
M. Hummer ◽  
G. Kemmler ◽  
I. Kurzthaler ◽  
A. Saria ◽  
...  
Keyword(s):  
Plasma Level ◽  
Coefficient Of Variation ◽  
Plasma Levels ◽  
Maintenance Treatment ◽  
Clinical Symptoms ◽  
Significant Degree ◽  
Individual Variability ◽  
Second Step

BackgroundPrevious studies of clozapine pharmacokinetics have shown a wide intra- and inter-individual variability of plasma levels in patients on stable clozapine doses. We investigated dose-plasma level relationships and intra-individual variability of plasma levels during maintenance treatment with clozapine.MethodForty-one patients on clozapine were followed for 26 weeks with repeated plasma level measurements and assessments of co-medication and clinical symptoms. In a second step, 15 patients on stable clozapine doses between treatment Weeks 12 and 52 were followed in the same way. Coefficient of variation was used as a parameter of plasma level deviation.ResultsDose-plasma level correlations stayed significant from Week 6 to Week 26 (n=41). The group of patients followed up to Week 52 showed a mean intra-individual coefficient of variation of 52.8% (s.d. =20.6), and remained stable psychopathologically.ConclusionsEven though clozapine plasma levels may show a significant degree of variation, this is not necessarily reflected in a change in psychopathology.

scholarly journals High doses of carbamazepine for refractory partial epilepsy

1996 ◽  
Vol 54 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Cristiana Borges Pereira ◽  
Carlos Otto Heise ◽  
Arthur Cukiert
Keyword(s):  
Side Effects ◽  
Plasma Level ◽  
Plasma Levels ◽  
Partial Epilepsy ◽  
The Other ◽  
Partial Seizures ◽  
High Doses ◽  
Higher Doses ◽  
Refractory Partial Epilepsy

Forty-eight patients with partial seizures were analysed during treatment with 1200 mg/d or more of carbamazepine (CBZ). Thirty-three were on monotherapy and fifteen on polytherapy. The other drugs were kept unchanged in the patients on polytherapy. The dose of CBZ was increased if no control was observed and the patient had no side effects. The doses used ranged between 1200 and 1900 mg/day (1200 mg/day, n=18; 1300mg/day, n=1; 1400 mg/day, n=7; 1600 mg/day, n=9; 1700 mg/day, n=4; 1800 mg/day, n=8; 1900 mg/day, n=1). Anticonvulsant plasma levels were taken to confirm patient compliance. The average plasma level was 9.6 ug/mL. The period of follow up varied from 3 to 96 months (M=25.6). Seizure's control was observed in 7 (14.48%) patients taking 1200 mg/day and in 2 (4.16%) patients taking 1400 mg/day of CBZ. Thirty-nine patients did not show any control (81.21%). Ten patients (20.81%) had signs of intoxication. When patients have no improvement with 1400 mg/day, it is difficult to obtain any control despite the use of higher doses of CBZ, which frequently expose the patient to significant side effects.

The Morality of Treating Patients with Depot Neuroleptics: the experience of community psychiatric nurses

2000 ◽  
Vol 7 (1) ◽  
pp. 35-46 ◽  
Author(s):  
Bodil Svedberg ◽  
Tore Hällström ◽  
Kim Lützén
Keyword(s):  
Phenomenological Study ◽  
Psychiatric Nurses ◽  
Neuroleptic Treatment ◽  
Best Interest ◽  
Treatment Situation ◽  
Community Psychiatric ◽  
Moral Aspect ◽  
Depot Neuroleptics ◽  
Depot Neuroleptic ◽  
Descriptive Method

The aim of this qualitative study was to gain an understanding of the meaning that community psychiatric nurses impart to their everyday interactions with patients in depot neuroleptic treatment situations. Nine experienced community psychiatric nurses were interviewed using semistructured, open-ended questions. Data analysis was by the phenomenological descriptive method according to Giorgi. Four themes were identified, highlighting aspects of the moral meaning of treating patients with depot neuroleptics: (1) ‘benevolent justification’ occurs when nurses perceive that the patient’s welfare is at stake; (2) ‘inability to advocate the patients’ best interest’ occurs when nurses feel they are at a disadvantage; (3) ‘accommodative interactions’ occur when nurses are able to respond to a patient’s expressed needs; and (4) ‘acceptable advocacy’ occurs when physicians are sensitive to nurses’ suggestions on patients’ treatment. The findings indicate that treatment care planning involving both patients and nurses is essential to enhance patients’ autonomy, which is a precondition for satisfactory interactions. This phenomenological study describes the meaning that nurses give to administering depot neuroleptic injections to patients in the context of community psychiatric clinics. The phenomenon of concern was identified as the moral aspect in the interactions with individual patients in the treatment situation.

Evidence for use of depot neuroleptic medication

2004 ◽  
Vol 21 (3) ◽  
pp. 95-99
Author(s):  
MacDara McCauley ◽  
Gerard Connolly
Keyword(s):  
Clinical Practice ◽  
Maintenance Treatment ◽  
Evidence Base ◽  
Neuroleptic Medication ◽  
Depot Antipsychotic ◽  
Depot Neuroleptics ◽  
Depot Neuroleptic

AbstractObjective:To review the evidence guiding conventional and atypical depot neuroleptic usage.Method:A search of biomedical electronic databases including Medline, Embase, PsychInfo and Cochrane was performed. Hand searching of journals was also carried out.Results:Depot neuroleptics are safe and effective in the maintenance treatment of patients with schizophrenia. There is some evidence to support the use of depot neuroleptics in illnesses other than schizophrenia. The evidence base guiding depot usage is sparse.Conclusions:Although guidelines are emerging there is a pressing need for rigorous well designed trials of depot antipsychotic usage. The advent of atypical depot antipsychotic preparations should stimulate research in this important area of clinical practice.

The Clinical Use of Plasma Clozapine Levels

1998 ◽  
Vol 32 (4) ◽  
pp. 567-574 ◽  
Author(s):  
Ron Bell ◽  
Andrew McLaren ◽  
Jason Gaianos ◽  
David Copolov
Keyword(s):  
Clinical Practice ◽  
Side Effects ◽  
Plasma Level ◽  
Clinical Response ◽  
Clinical Effect ◽  
Relevant Literature ◽  
Clinical Use ◽  
Good Clinical Response ◽  
Daily Dose ◽  
Comprehensive Search

Objective: This review examines the evidence supporting the proposition that a threshold clozapine plasma level can predict clinical response. In addition, it provides a brief overview of the pharmacokinetics, side effects, drug interactions and assay methodology of clozapine. Method: A comprehensive search of relevant literature was made with respect to the above criteria. The findings were collated and analysed to produce an overview of the usefulness of using clozapine levels in clinical practice. Results: Most researchers find that, although the correlation between dose of cloza pine and clinical effect is not high, a threshold plasma level of 350–420 ng mL of clozapine is associated with an increased probability of a good clinical response to the drug. Results vary, however, with the study design. Conclusions: The data reviewed present a case for increasing the dose of cloz apine in non-responsive patients to achieve a plasma level of at least 350–420 ng mL−1. Non-response at these levels, however, should not preclude a further upward titration of dose. This should occur unless (i) clinical response is obtained at a lower dose, (ii) intolerable side effects occur, or (iii) a daily dose of 900 mg is reached.

scholarly journals Interest of Fluvoxamine as an Add-On to Clozapine in Children With Severe Psychiatric Disorder According to CYP Polymorphisms: Experience From a Case Series

2021 ◽  
Vol 12 ◽  
Author(s):  
Camille Berel ◽  
Ulysse Mossé ◽  
Julien Wils ◽  
Lauriane Cousin ◽  
Laurent Imbert ◽  
...  
Keyword(s):  
Side Effects ◽  
Plasma Level ◽  
Psychiatric Disorder ◽  
Drug Interactions ◽  
Psychiatric Disorders ◽  
Plasma Levels ◽  
Case Series ◽  
A Minor ◽  
Enzymatic Inhibitor ◽  
Cyp Inhibitors

Despite its drastic efficacy in resistant psychiatric disorders, clozapine remains rarely used in youth due to its side effects. Clozapine plasma level is determined through its metabolism involving several isoforms of cytochromes 450 (CYP450) family. Isoform CYP1A2 appears as a limiting enzyme involved in the metabolism of clozapine, while isoforms 2C19, 2D6, 3A4, and 3A5 also contribute in a minor way. Clozapine efficacy is limited by a significant inter-patient variability in exposure according to CYP's polymorphisms. Clozapine plasma levels may be increased with CYP inhibitors such as fluvoxamine. This drug is a potent enzymatic inhibitor of CYP1A2 and, to a lesser extent, of CYP3A4 and CYP2D6. Hence, in case of CYP's polymorphisms in youth, the use of fluvoxamine as add-on to clozapine could help in reaching clinical and biological efficacy and allowing lower clozapine dosage and a better tolerance profile as it has already been described in adults. We report four pediatric cases with severe psychiatric disorders underlying our experience with CYP polymorphism explorations and the use of fluvoxamine as add-on to clozapine. Our four patients clinically improved after the introduction of fluvoxamine, enhancing clozapine metabolism and therefore the clozapine plasma level within therapeutic range. Despite the interesting results of fluvoxamine, we report a severe issue of tolerance for one patient, emphasizing the need for caution regarding possible drug interactions when fluvoxamine is considered. Hence, we propose a detailed step-by-step multidisciplinary protocol.

Nortriptyline Plasma Levels and Subjective Side Effects*

1978 ◽  
Vol 132 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Vincent E. Ziegler ◽  
John R. Taylor ◽  
Richard D. Wetzel ◽  
John T. Biggs
Keyword(s):  
Side Effects ◽  
Plasma Level ◽  
Plasma Levels ◽  
Tricyclic Antidepressants ◽  
Dry Mouth ◽  
Severity Of Depression ◽  
The Common ◽  
Pre Treatment ◽  
The Individual ◽  
Subjective Side

Nortriptyline plasma levels and the incidence and severity of the common subjective side effects of the tricyclic antidepressants were determined in 26 patients during six weeks of treatment with nortriptyline. The total corrected (treatment minus pre-treatment) score of the eight side effects most independent of the severity of depression correlated (0 · 60) with the nortriptyline plasma level. Increased perspiration (o · 59) and dry mouth (o · 54) were the individual corrected side effects which most consistently correlated with the plasma level. These subjective side effects may serve as clinically useful guides to dosage adjustments during treatment, though their value is limited by the magnitude of the correlations and the need to correct for their presence prior to treatment.

Rapamycin Has Biological Activity in a Subset of Patients with Myelodysplastic Syndrome - Results of a Phase I/II Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1449-1449
Author(s):  
Uwe Platzbecker ◽  
Michael Haase ◽  
Regina Herbst ◽  
Anette Hanel ◽  
Karsten Voigtmann ◽  
...  
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
Plasma Level ◽  
Myelodysplastic Syndrome ◽  
Phase I ◽  
Plasma Levels ◽  
Immune Surveillance ◽  
Therapeutic Benefit ◽  
Significant Difference ◽  
Median Plasma

Abstract The pathophysiology of myelodysplastic syndrome (MDS) involves disturbed regulation of angiogenesis, apoptosis, proliferation and differentiation as well as immune surveillance. There is increasing evidence that rapamycin (sirolimus) might affect these pathways positively thus possibly being of therapeutic benefit in patients with this disease. These data prompted us to perform a phase I/II study to evaluate the safety and efficacy of rapamycin in the treatment of patients with MDS. Nineteen patients (median age 72 years) diagnosed with MDS according to the WHO classification received rapamycin orally with a target blood concentration of 3–12 ng/ml. Rapamycin was administered for a median of 3.7 months (range 0.3–11). Three patients (1 x RAEB-2, 1 x RAEB-1, 1 x RCMD) showed either a major (1 x platelet, 1 x neutrophil) or a minor (1 x erythroid, 2 x platelet) hematological response according to the IWG criteria. There was no statistically significant difference in the rapamycin plasma levels between the three responders (median plasma level 3.62, range 1.63–4.39) and non-responders (median plasma level 4.22, range 2.81–7.4). Major side effects were hyperlipidemia (n=4), stomatitis (n=3), thrombocytopenia (n=2) and urinary tract infection (n=1). Study medication had to be stopped due to side effects in five patients (26 %), one of them being a responder to rapamycin. Plasma levels of rapamycin were not elevated in patients experiencing toxicity. Taken together these data demonstrate that rapamycin might have biological activity in patients with rather advanced MDS. New and possibly less toxic analogues of rapamycin are currently developed. They could be candidates for future trials in patients with MDS.

scholarly journals Patients' knowledge and views of their depot neuroleptic medication

1999 ◽  
Vol 23 (8) ◽  
pp. 467-470 ◽  
Author(s):  
R. Goldbeck ◽  
S. Tomlinson ◽  
J. Bouch
Keyword(s):  
Mental Health ◽  
Side Effects ◽  
Health Centre ◽  
Clinical Implications ◽  
Community Mental Health Centre ◽  
Neuroleptic Medication ◽  
Mental Health Centre ◽  
Depot Neuroleptic ◽  
Attitudes And Knowledge

Aims and methodThis study examined the attitudes and knowledge of patients regarding their depot neuroleptic medication. All patients were attending a community mental health centre in Clydebank, Scotland.ResultsMany patients had limited knowledge of their medication, its benefits and side-effects as well as the rationale for its use. The biggest gaps were found in patients' knowledge of the long-term side-effects of their medication.Clinical implicationsOur findings raise doubts as to the capacity of some patients to give informed consent to their treatment. A number of steps are outlined in order to raise patients' standard of knowledge.

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